Abstract
Background Cortical hyperexcitability is an important pathophysiological mechanism in amyotrophic lateral sclerosis (ALS). The direction of transcranial magnetic stimulation (TMS) stimulus within the primary motor cortex influences descending corticospinal volleys to thereby provide information about distinct interneuronal circuits.
Methods Cortical motor function and cognition was assessed in 29 ALS patients with results compared to healthy volunteers. Cortical dysfunction was assessed using threshold-tracking TMS to explore alterations in short interval intracortical inhibition (SICI) and short interval intracortical facilitation (SICF) using a figure-of-eight coil with the coil oriented relative to the primary motor cortex in a posterior-anterior (PA), lateral-medial (LM), and anterior-posterior (AP) direction.
Results Mean SICI, between interstimulus interval (ISI) of 1-to-7ms, was significantly reduced in ALS patients compared to healthy controls with the coil oriented in PA (P=0.044) and LM (P=0.005) but not the AP (P=0.08) directions. A significant correlation between mean SICI oriented in a PA direction and the total Edinburgh Cognitive and Behavioural ALS Screen score (Rho=0.389, P =0.037) was evident. In addition, the mean SICF, between ISI 1-to-5ms, was significantly increased in ALS patients when recorded with TMS coil oriented in PA (P=0.035) and LM (P<0.001) directions but not AP direction (P=0.482).
Conclusion The present study has established that dysfunction of distinct interneuronal circuits mediates the development of cortical hyperexcitability in ALS. The mechanisms that underlie dysfunction of these specific cortical neuronal circuits will enhance understanding of the pathophysiological processes in ALS, with the potential to uncover novel therapeutic targets.
